大鼠血浆中B7011含量LC-MS/MS测定条件的确立及其在大鼠体内的药代动力学特点  

Determination of B7011 in rat plasma by liquid chromatography mass spectrometer and its pharmacokinetic characteristics

作　　者：柳艳青[1] 韩晓彤 王元桦 朱辉 孔琦[1] 关勇彪[1] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850 [2]成都雅途生物科技有限公司,成都610041

出　　处：《中国药理学与毒理学杂志》2014年第4期575-579,共5页Chinese Journal of Pharmacology and Toxicology

摘　　要：目的：建立灵敏、专一的测定大鼠血浆中 B7011含量的液相色谱质谱联用仪（LC-mS/ mS）检测方法。方法采用甲醇沉淀蛋白质的方法对血浆样品进行前处理，对方法的线性范围、批内和批间精密度、特异性、基质效应、回收率、准确度和稳定性等指标进行确证，并检测了 SD 大鼠单次静脉注射 B70110.5 mg·kg-1的血药浓度。结果血浆 B7011在30~20000μg·L-1浓度范围内线性良好，定量下限为30μg·L-1；B701160，1000，16000和10000μg·L-1血浆浓度测定的批内精密度分别为5.61%~13.31%，2.31%~8.35%，2.02%~9.47%和4.0%~15.0%，批间精密度分别为10.05%，2.55%，3.75%和8.58%；B701160，1000和16000μg·L-1的回收率为114.12%，109.2%和101.06%；浓度为200，1000，10000和100000μg·L-1的 B7011血浆标品在4℃放置4 h 和-20℃冻存10 d（期间反复冻融3次）的条件下存放稳定。静脉注射 B7011在雌雄大鼠的主要动力学参数：峰浓度分别为8373.28和8564.59μg·L-1；曲线下面积分别为98400和104000μg·L-1·h；消除半衰期分别为41.7和63.6 h。结论建立了大鼠血浆中B7011含量测定的 LC-mS/ mS 方法，能够满足其药代动力学和毒代动力学研究的需要。OBJECTlVE To estabIish a simple,sensitive and quick method for determination of B7011 in rat plasma. METHODS The method of protein precipitation with methanol was used for pre-treatment of plasma samples determined by Iiquid chromatography mass spectrometer. The Iinear rela-tionship,intra-batch and inter-batch precision,specificity,matrix effect,recovery rate,the accuracy and stability of the plasma samples were vaIidated. The concentration of B7011 in plasma was determined by LC-mS/ mS following a singIe intravenous injection of B7011 0.5 mg·kg-1 to rats. RESULTS The Iinear range of B7011 was 30-20 000 μg·L-1 ,the Iower Iimit of quantification was 30 μg·L-1 in plasma,the in-tra-batch precision of 60,1000,16 000 and 10 000 ng·mL-1 was 5.61% -13.31%,2.31% -8.35%, 2.02%-9.47% and 4.0%-15.0% respectively,and inter-batch precision was 10.05%,2.55%,3.75% and 8.58% respectively. The recovery of 60,1000,and 16 000 μg·L-1 was 114.12%,109.2% and 101.06%respectively. The average peak concentrations were 8373.28 and 8564.59 μg·L-1 ,the mean AUC was 98 400 and 104 000 μg·L-1·h and the t1/ 2z for B7011 was 41.7 and 63.6 h in bIood of maIe and femaIe rats, respectively. CONCLUSlON The estabIished method is sensitive, fast and simple and concentration of B7011 in plasma is determined by LC-mS/ mS following a singIe intravenous injection of B7011 0.5 mg·kg-1 to rats. It can satisfy the requirements of pharmacokinetic and toxicokinetic studies.

关 键 词：B7011 液相色谱质谱 药代动力学 

分 类 号：R965.2[医药卫生—药理学]